(2E,4E,6E,10E)-3,7,11,15-Tetramethyl-2,4,6,10,14-hexadecapentaenoic acid, a class of polyprenyl compound, is known to have an action for activating transcription mediated through retinoic acid receptors as well as an action for inducing differentiation and apoptosis in hepatocellular carcinoma. Clinically, it has been reported that (2E,4E,6E,10E)-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid significantly suppressed recurrence after radical cure of hepatoma by long-term administration for one year, indicating an inhibitory action against recurrence of hepatoma, and that almost no side effect is observed such as dysfunction of liver and those with other retinoids (N. Eng. J. Med. 334,1516 (1996)).
As for method for preparing (2E,4E,6E,10E)-3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid, which is a known compound, the compound is prepared, for example, by using compound A as a synthetic intermediate. The compound A is prepared, for example, by reacting compound B and (2E,6E)-3,7,11-trimethyl-2,6,10-dodecatrien-1-al (for example, see, Japanese Patent Publication (Kohyo) Nos. 63-32058 (1988) and 63-34855 (1988)). [In the aforementioned general formula, each of R3 and R4 represents an alkyl group.]
However, the above method has disadvantages such as a side production of a large amount of undesired Z-form compounds. Therefore, the development of a method for preparing the E-form compound has been desired which is highly selective and practically applicable.
Generally, as a selective preparation an isomer by using Wittig reaction, a method is known wherein one equivalent or a large excess amount of a crown ether is added to a reaction system (for example, see, J. Chem. Soc., Perkin Trans. 1, 2073 (2000) and Tetrahedron Lett., 24, 4405 (1983)). However, industrial applications of the method are limited because crown ethers are expensive.
A method wherein a catalytic amount of a crown ether is used for selective preparation of an isomer is also reported (for example, see, Agric. Biol. Chem., 45, 1461 (1981), Yingyong Huaxue, 5, 70 (1988), Synthesis, 784 (1975)). However, industrial applications of the method are also limited because the method involves a reaction at a temperature of as low as −40° C. or as high as 80° C. or more, and the method achieves insufficient selectivity.
A method wherein a crown ether is used in a catalytic amount for selective preparation of a styrene derivative is also reported (for example, see, Tetrahedron Lett., 37, 4225 (1996), Synthesis, 278 (1975)). However, the method fails to give a sufficient result of Wittig reaction for an aliphatic aldehyde, or the document neither teaches nor suggests said reaction.
In addition, a method wherein an isomer is selectively prepared by using a catalytic amount of a crown ether and trialkyl-3-methyl-4-phosphonocrotonate as a Wittig reagent (for example, see, Izv. Akad. Nauk SSSR, Khim. 2544 (1990), Izv. Akad. Nauk SSSR, Khim. 2382 (1988), Izv. Akad. Nauk SSSR, Khim. 2377 (1988)). However, industrial applications of the method are limited because the method has a problem of insufficient selectivity.